The microflora of the human large intestine (typically divided into caecum, colon and rectum) plays a crucial role in both human nutrition and health. The bacterial composition is influenced and can be modulated by dietary intake. Carbohydrates which have passed through the stomach and small intestine are metabolised by the bacteria and as a major end-product of metabolism short-chain fatty acids (SCFA), such as acetate, propionate, butyrate and valerate, are formed, which are subsequently released into the blood. Other end products of bacterial fermentation include for example lactate and succinate. The total amounts and compositions (relative amounts) of these end products in turn have a profound effect on bacterial growth, pH, exclusion of pathogenic species, etc. A method to beneficially influence the microbial flora and human health is the administration of prebiotics. “Prebiotics” were defined as “non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improve the hosts health (Gibson and Roberfroid 1995, J. Nutr. 125, 1401-1412). The criteria which a compound must fulfil in order to be classified as a prebiotic are: 1) it must not be hydrolysed or absorbed in the upper part of the gastrointestinal tract (stomach, small intestine), 2) it must be selectively fermented by one or more potentially beneficial bacteria in the colon, 3) it must alter the colonic microbiota towards a healthier composition and 4) it must preferably induce effects which are beneficial to the health of the subject. Commonly used prebiotics are so-called non-digestible carbohydrates (or “soluble dietary fibres”), which pass undigested through the upper part of the gastrointestinal tract into the large intestine. These include for example fructooligosaccharides (FOS), oligofructose, inulin and transgalacto-oligosaccharides (TOS). It should be noted that in the literature, there is often inconsistency between the use of various terms, such as fructooligosaccharide, inulin, oligofructose and inulo-oligosaccharides, and the same term may be used for different compounds or compositions.
Well known beneficial bacteria, which are stimulated by the uptake of prebiotics, are lactic acid bacteria, such as Lactobacilli and Bifidobacteria, and health benefits have been ascribed to be due to this stimulatory effect. For example, beneficial effects of inulin and inulin-type fructans, such as oligofructose, on intestinal function have been described (Jenkins et al. 1999, J. Nutrition 129, 1431S-1433S) and this effect is thought to be due to a bifidogenic effect, which refers to a selective growth stimulating effect on total bifidobacteria, measured either in vivo through bifidobacterial counts of the faeces or in vitro (see e.g. Roberfroid, Am J Clin Nutr 2001, 73(suppl), 406S-409S).
Human milk appears also to have a bifidogenic effect, as the dominant bacteria which become established in breast-fed infants are bifidobacteria. In contrast, bacterial colonisation of milk formula fed infants is not dominated by bifidobacteria and is more diverse in bacterial species (Harmsen et al. 2000, J. Pediatr. Gastroenterol. Nutr. 30, 61-67). It is thought that oligosaccharides found in the human milk are responsible for the bifidogenic or prebiotic effect and efforts have been made to modify infant formula in such a way that it resembles human milk as closely as possible and especially that it has the same or a very similar prebiotic effect as human milk. This has been done by adding prebiotics to infant milk formula (Boehm et al. Acta Paediatr. Suppl. 2003, 441, 64-67 and Moro et al. 2002, J Pediatr Gastroenterol Nutr 34, 291-295). For example, supplementation of bovine milk formula with an oligosaccharide mixture comprising trans-galactooligosaccharides (TOS) and inulinHP has been described to increase the faecal count of bifidobacteria in bottle fed infants (Boehm et al. 2002, Arch Dis Child 86, F178-F181).
Also, supplementation of infant milk formula with TOS and inulin has been described to have a bifidogenic effect, and to decrease faecal pH (Boehm et al. 2003 supra; Moro et al. 2003, Acta Paediatr. Suppl. 441:77-79; Marini et al. 2003, Acta Paediatr. Suppl. 441:80-81; Boehm et al. 2002, Arch. Dis. Child Fetal. Neonata. Ed. 86:F178-F181; Moro et al. 2002, J. Pediatr. Gastroenterol. Nutr. 34:291-295; Schmelzle et al. 2003, J Pediatr. Gastroenterol. Nutr. 36:343-51).
Upon fermentation of prebiotics by lactic acid bacteria organic acids are produced and the pH is lowered. Lactobacilli produce either lactate or lactate and acetate (a Short Chain Fatty Acid; SCFA). The lactate can be in the L- or D-form. Bifidobacteria, on the other hand, produce L-lactate and acetate, but no D-lactate. Bifidobacteria (and other lactic acid bacteria) usually do not lead to the production of gases, such as H2 and CH4. They also do not produce other SCFA, such as propionate, butyrate, isobutyrate, valerate and isovalerate. The presence of SCFA, such as isobutyrate and isovalerate, are indicative of the fermentation of carbohydrates by other bacterial species, such as Clostridia and Bacteroides or Enterobacteriaceae, or are indicative for the fermentation of proteins (of which the Bifidobacteria have a poor capability). Also, other intestinal bacteria are capable of producing acetate or lactate, such as Propionibacteria, Enterococci and Pediococci.
Previously it has been reported that the intake of certain prebiotic carbohydrates increase the (relative) amounts of Bifidobacteria and/or Lactobacilli. Concomitantly an increased formation of SCFA and decrease of pH has been observed. But also the formation of gases, which results in unwanted symptoms such as flatulence and abdominal pain, has been reported when introducing prebiotics, such as inulin or GOS, into the diet. Furthermore, not only acetate but also increases in, for example, butyrate have been reported, which is undesirable. A range of undesirable effects have therefore been described, resulting from the consumption of nutrition supplemented with certain prebiotics.
In the colon and faeces of breast fed infants the predominant SCFA found is acetate. Furthermore high concentrations of lactate are found. These (relative) amounts are higher than those observed in adults (where concentrations of lactate are generally negligible) or in standard milk formula fed infants. Subsequently, concentrations of propionate and especially butyrate are much lower in the colon and faeces of breast fed infants than in adults and even lower than in infants fed with standard infant milk formula. The pH of the faeces is lowest in breast fed children. As mentioned above, it is desirable to provide nutrient compositions, especially milk formula compositions, which, when consumed, result in an intestinal microflora closely resembling that of breast fed infants.
Many health effects of SCFA and lactate and a low colon pH have been described. The lowered pH and the presence of organic acids have been described to have an anti-pathogenic effect, and provide an advantage to acid tolerant bacteria such as the lactic acid bacteria (including Bifidobacteria). Also effects of SCFA on the intestinal wall have been described. SCFA are an energy source of colonocytes and thereby aid to the intestinal barrier integrity. SCFA are also involved in effects on peristalsis, bile acid metabolism, water absorption and cell differentiation (see e.g. EP1105002). SCFA are known to stimulate the production of mucus and are involved in mineral absorption and mucus production.